Résumé
<p><b>OBJECTIVE</b>To investigate the transcriptional regulation of pacemaker channel I(f) mediated by vasoactive peptide endothelin-1 (ET-1) in neonatal rat ventricular myocytes and its mechanism.</p><p><b>METHODS</b>Neonatal rat ventricular myocytes were enzymatically isolated. I(f) current was recorded using the whole-cell patch-clamp technique. The expression of hyperpolarization-activated cyclic nucleotide-gated channel (HCN) isoforms HCN2 and HCN4 were measured by quantitative RT-PCR.</p><p><b>RESULTS</b>ET-1 increased the expression of HCN2 and HCN4 mRNA in a dose- and time-dependent manner. These effects were blocked by specific ETA receptor antagonist BQ-123 but not the ETB receptor antagonist BQ-788. The effects of ET-1 on HCN2 and HCN4 mRNA expression were not affected by the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB-203580).</p><p><b>CONCLUSION</b>These findings indicate that ET-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes via ETA receptor through a p38 MAPK-independent signaling pathway, which might be linked to the intrinsic arrhythmogenic potential of ET-1.</p>
Sujets)
Animaux , Rats , Animaux nouveau-nés , Canaux cationiques contrôlés par les nucléotides cycliques , Endothéline-1 , Métabolisme , Imidazoles , Pharmacologie , Myocytes cardiaques , Métabolisme , Oligopeptides , Pharmacologie , Techniques de patch-clamp , Pipéridines , Pharmacologie , Pyridines , Pharmacologie , Rat Sprague-Dawley , Transduction du signal , p38 Mitogen-Activated Protein Kinases , MétabolismeRésumé
In regional anatomy the appliance of the methods of problem based learning can cultivate students' practical ability,slimulate their motivity and raise their passion for study.It is also effective to improve their capabilities of self-study,cooperation,as well as analizing and solving problems.